Disease relevance of C11766

• Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine [1].
• The less severe worsening of cognition after withdrawal of treatment in patients previously treated with rivastigmine suggests an effect on disease progression [2].
• These data show that the reduction by Rivastigmine of the immediate and long-term sequelae of brain injury are mediated by increased cholinergic activity at both muscarinic and nicotinic receptors [3].
• Rivastigmine (2 mg/kg) reduced cerebral edema by at least 50% (p < 0.01), 24 h after CHI and accelerated the recovery of motor function 7 and 14 days after CHI [3].
• For some cholinesterase inhibitors, such as rivastigmine, the cholinergic adverse effects such as nausea, vomiting, dizziness, diarrhoea and abdominal pain can be reduced by slowing the rate of dose titration [4].

Psychiatry related information on C11766

• Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study [5].
• FINDINGS: Patients taking rivastigmine were significantly less apathetic and anxious, and had fewer delusions and hallucinations while on treatment than controls [5].
• Compared to placebo, rivastigmine produced only a small and non-significant improvement in task accuracy across all conditions with no change in response latency, and increased activity in the extrastriate visual cortex in areas associated with visual and spatial attention but not in any region within the working memory network [6].
• Rivastigmine also inhibits BuChE, which could lead to additional benefits in late-stage Alzheimer's disease, but also cause more GI side effects at initiation of therapy [7].
• RESULTS: For the group of patients as a whole, there was a significant improvement in short term memory and orientation during rivastigmine treatment [8].

High impact information on C11766

• Treatment aimed to restore acetylcholine content through chronic administration of selective acetylcholinesterase inhibitors (rivastigmine and donepezil) restores cognitive performance, choline acetyltransferase activity, and nerve growth factor mRNA expression [9].
• Some studies evaluated cholinesterase inhibition in vivo with PET (Positron Emission Tomography) with higher reductions for rivastigmine than for donepezil in several cortical areas [10].
• CONCLUSIONS: Rivastigmine causes persistent inhibition of AChE and BuChE in CSF as well as plasma [11].
• OBJECTIVE: To study the long-term dual inhibitory effects of rivastigmine on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in patients with AD [11].
• The cholinesterase inhibitors rivastigmine, donepezil, and metrifonate, which are devoid of nicotinic APL action, did not affect synaptic transmission [12].

Chemical compound and disease context of C11766

• Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer's disease [13].
• OBJECTIVE: To evaluate retrospectively whether rate of disease progression during placebo treatment affects response to subsequent rivastigmine tartrate therapy for patients with mild to moderately severe AD [14].
• Indeed, three compounds have received European approval for the treatment of the cognitive symptoms of Alzheimer's disease, first tacrine and more recently, donepezil and rivastigmine, all of which are cholinesterase inhibitors [15].
• The neuroprotective effects of Rivastigmine on brain edema, neurological and motor function, and performance in the Morris water maze were completely antagonized by simultaneous SC injection of either scopolamine (0.5 mg/kg) or mecamylamine (2.5 mg/kg) [3].
• In the present study, we analyzed the antiamnesic and neuroprotective activities of donepezil in a mouse hypoxia model induced by repetitive CO exposure, comparing donepezil's pharmacological profile with other cholinesterase inhibitors tacrine, rivastigmine, and galanthamine, and the reference sigma1 agonist igmesine [16].

Biological context of C11766

• CONCLUSION: A noncompartmental approach and a compartmental approach based on a population pharmacokinetic model with Michaelis-Menten elimination yielded comparable values, 71.7% and 60.2% respectively, for the absolute bioavailability of a single 6 mg oral dose of rivastigmine [17].
• Plasma concentrations of the major metabolite, NAP 226-90, formed by the hydrolysis of rivastigmine by cholinesterase are lower than those of the parent compound following oral and intravenous administration [17].
• Donepezil and tacrine are highly protein bound, whereas protein binding of rivastigmine and galantamine is less than 40% [18].
• In contrast, concomitant medication with various drugs with rivastigmine does not seem to cause any drug interactions in patients with Alzheimer's disease [4].
• CONCLUSIONS: MTLA and the APOE genotype are not clinically useful predictors of cognitive response in subjects with probable AD who are treated with rivastigmine [19].

Anatomical context of C11766

• Preferential cerebrospinal fluid acetylcholinesterase inhibition by rivastigmine in humans [20].
• Rivastigmine (0.75 and 1.5 mg/kg) and physostigmine (0.05 mg/kg) caused significantly greater ChE inhibition in females than in males (P<0.01) in the cerebral cortex, hippocampus and striatum, but not in the periphery 30 and 60 min after injection [21].
• In contrast, short latency afferent inhibition from the median nerve was significantly increased by the administration of rivastigmine [22].
• This study compared the effect of rivastigmine on cholinesterase (ChE) activity in different brain regions, heart, skeletal muscle and plasma and on the cognitive impairment induced by scopolamine (0.5 mg/kg) in male and female rats [21].
• Rivastigmine antagonizes deficits in prepulse inhibition induced by selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis [23].

Associations of C11766 with other chemical compounds

• The objective of this study was to evaluate the rate and extent of absorption and metabolism of rivastigmine (Exelon), ENA 713) after site-specific delivery of the drug in the gastrointestinal (GI) tract using a naso-intestinal intubation technique [24].
• Cerebral glucose metabolism, cerebrospinal fluid-beta-amyloid1-42 (CSF-Abeta42), tau and apolipoprotein E genotype in long-term rivastigmine and tacrine treated Alzheimer disease (AD) patients [25].
• Serotonin depletion results in a decrease of the neuronal activation caused by rivastigmine in the rat hippocampus [26].
• No degradation was observed for Rivastigmine hydrogen tartrate except in base hydrolysis and the formed degradation product was found to be Imp 1 [27].
• Baseline scores of global response, cognition, word fluency and activities of daily living were maintained in patients receiving rivastigmine, and there was no increase in benzodiazepine or neuroleptic intake [28].

Gene context of C11766

• Recently, rivastigmine, a novel cerebral selective cholinesterase-inhibitor (ChEI), was shown to be a powerful drug to enhance GH release to repeated GHRH stimulation in healthy elderly human subjects [29].
• Analysis of response by BuChE genotype suggests that this differential effect may be due to the inhibition of BuChE, in addition to AChE, by rivastigmine [30].
• Rivastigmine is not metabolised via CYP enzymes, but via esterases and is excreted in the urine [4].
• Medial temporal lobe atrophy and APOE genotype do not predict cognitive improvement upon treatment with rivastigmine in Alzheimer's disease patients [19].
• There is substantial evidence that the cholinesterase inhibitors, including donepezil, galantamine and rivastigmine, decrease acetylcholinesterase activity in a number of brain regions in patients with Alzheimer's disease [31].

Analytical, diagnostic and therapeutic context of C11766

• Neural correlates of adjunctive rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind fMRI study [6].
• Donepezil, rivastigmine and galantamine had showed similar efficacy according to meta-analysis from randomised clinical trials [10].
• RESULTS: Following oral administration of a single 6 mg capsule, rivastigmine is rapidly absorbed with an average time to peak plasma concentration of about 1 hour and an average peak concentration of about 25.6 g/L [17].
• By a noncompartmental approach, the absolute bioavailability of the 6 mg oral dose of rivastigmine was 71.7% when compared with a 2mg intravenous infusion normalised for dose [17].
• OBJECTIVES: To predict the treatment response to rivastigmine in patients with Alzheimer's dementia using neuropsychological and EEG data [8].

References